Prostaglandin E.sub.2 (abbreviated as PGE.sub.2 hereafter) has been known as metabolite in the arachidonate cascade. It has been known that PGE.sub.2 has cyto-protective activity, uterine contractile activity, a pain-inducing effect, a promoting effect of digestive peristalsis, an awakening effect, a suppressive effect of gastric acid secretion, hypotensive activity and diuretic activity etc.
In a recent study, it was found that PGE.sub.2 receptor was divided into some subtype which possess different physiological roles from each other. At present four receptor subtypes are known and they are called as EP.sub.1, EP.sub.2, EP.sub.3 and EP.sub.4 (Negishi M. et al, J. Lipid Mediators Cell Signaling, 12, 379-391 (1995)).
The present inventors investigated to find new compounds which bind on each receptor specifically, we found that the compounds of the present invention could bind strongly on EP.sub.2 subtype receptor and achieved the present invention.
The compounds of the formula (I) of the present invention possess a binding activity for EP.sub.2 subtype receptor strongly. Therefore, they are useful for prevention and/or treatment of immunologic diseases (autoimmune diseases, organ transplantation, etc.), asthma, abnormal bone formation, neuronal cell death, liver damage, abortion, premature birth or retina neuropathy of glaucoma etc.
Among the compounds of the present invention of the formula (I), compounds which bind weakly on receptor subtypes except for EP.sub.2 and another arachidonic acid metabolism receptor (thromboxane receptor, PGI.sub.2 receptor, etc.) do not exhibit other effects and therefore, it is thought that such compounds will be useful as medical agents which have less side-effects.
On the other hand, many patent applications of PG derivatives are known. The following application is mentioned for-example.
In the specification of U.S. Pat. No. 4,132,738, a compound of the formula (A) ##STR3## wherein R.sup.1 and R.sup.2A is hydrogen atom;
R.sup.3A is hydrogen atom, or together with R.sup.4A is a methylene chain of 4 carbon atoms such that a cycloalkyl of 6 carbon atoms inclusive is formed, or together with R.sup.4A is a bicycloalkenyl or bicycloalkyl moiety having the formula ##STR4## (in which pA is an integer having a value of from 0 to 1 and qA is an integer having a value of from 2 to 3 and wherein the double bond of such bicycloalkenyl is in the qA bridge);
R.sup.4A together with R.sup.3A forms a cycloalkyl or bicycloalkyl or bicycloalkenyl as defined above, or together with R.sup.5A is a methylene chain of 3 carbon atoms such that a cycloalkyl of 4 carbon atoms inclusive is formed;
R.sup.5A is hydrogen atom, or together with R.sup.4A forms a cycloalkyl as defined above; and
R.sup.6A is hydrogen atom or straight-chain alkyl having from 1 to 8 carbon atoms; are disclosed as having an inhibitory activity on prostaglandin like.